Novel 3,6-unsymmetrically disubstituted-1,2,4,5-tetrazines: S-induced one-pot synthesis, properties and theoretical study

Article abstract of DOI:10.1039/c4ra10808f

18 unprecedented tetrazines unsymmetrically substituted at C3 and C6 by an aromatic heterocycle have been successfully prepared by the S-induced reaction of aromatic nitriles with hydrazine hydrate under thermal conditions. The spectral property investiga

Full text of DOI:10.1039/c4ra10808f

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Novel 3,6-unsymmetrically disubstituted-1,2,4,5-
tetrazines: S-induced one-pot synthesis, properties
and theoretical study†
Cite this: RSC Adv., 2015, 5, 12277
a
a
ab
a
a
a
Chen Li,‡ Haixia Ge,‡ Bing Yin, Mengyao She, Ping Liu,* Xiangdong Li
a
and Jianli Li*
18 unprecedented tetrazines unsymmetrically substituted at C3 and C6 by an aromatic heterocycle have
been successfully prepared by the S-induced reaction of aromatic nitriles with hydrazine hydrate under
thermal conditions. The spectral property investigation suggests that compounds 4d, 4e, 4f, 4p, 4q, 4r,
and 4v can display intense fluorescence in the visible region, and their fluorescent properties are
affected by the substituents both in tetrazine and in phenyl rings. Moreover, the electrochemical
behaviors of these synthesized tetrazines are demonstrated to be fully reversible. Furthermore, density
functional theory (DFT) calculations for these compounds were performed to investigate their optimized
structures, Fukui function and reactivity or selectivity in the inverse electron demand Diels–Alder reaction.
Received 19th September 2014
Accepted 14th January 2015
DOI: 10.1039/c4ra10808f
www.rsc.org/advances
can served as pesticides, herbicides and anti-inammatory,
Introduction
16–19
antimalarial drugs (Fig. 1).
Among many reported 1,2,4,5-tetrazine derivatives, the 3,6-
20
Since 1,2,4,5-tetrazine was rst reported by Hantzsch and Leh-
1
mann in 1900, studies of 1,2,4,5-tetrazine and its 3,6-disub- symmetrically disubstituted ones are common due to their
1b,13,21
stituted derivatives have received considerable attention due to synthetic accessibility.
In contrast, the reported 3,6-
their denitely unique skeleton and chemical/physical proper- unsymmetrically disubstituted-1,2,4,5-tetrazines are limited,
ties, and special application potential in the elds of industry, and especially their substituents at C3 and C6 positions are
2,3
agriculture and medicine.
The 1,2,4,5-tetrazine ring system, which consists of an lthio, methoxycarbonyl and methylsulnyl).
usually the alkyl and some specic substituent groups (methy-
11a,21,22
Furthermore,
electron-decient aromatic heterocycle with four nitrogens, is 3,6-unsymmetrically disubstituted-1,2,4,5-tetrazines with the
known for its high colour, biological activity and electrical aromatic heterocyclic substituents at C3 and C6 have rarely
property. And this system can be applied to biocompatible been reported. In addition, it is known that the substituents
4
5
6
labelling agents, sensors, on/off uorescence switching, live have an important effect on biological activities and chemical/
7
8
cell imaging, and components in photovoltaic cells. Addi- physical properties of compounds. For 3,6-unsymmetrically
tionally, the 1,2,4,5-tetrazines typically have high positive disubstituted-1,2,4,5-tetrazines, the aromatic heterocyclic
enthalpies of formation and high densities, which are suitable substituents at C3 and C6 will have the more signicant effect
for the development of energetic materials with desirable on their spectral and electrochemical properties. Therefore,
9,10
properties, such as explosive, propellant and pyrotechnics.
such 1,2,4,5-tetrazine derivatives may be served as potential
As the good electron acceptors, 1,2,4,5-tetrazine derivatives materials with special properties. Based on this aim, we have
can be used as 4-p components in inverse-type Diels–Alder
1
1
12
reactions, and provide an access to many heterocycles and
13
natural products. Furthermore, 1,2,4,5-tetrazine derivatives
exhibit various biological activities such as antibacterial, anti-
viral and antitumor properties,
2,14,15
therefore these compounds
a
College of Chemistry & Materials Science, Northwest University, Xi'an 710069, P. R.
China. E-mail: lijianli@nwu.edu.cn; liuping@nwu.edu.cn
b
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China
†
Electronic supplementary information (ESI) available. CCDC 973196. For ESI
and crystallographic data in CIF or other electronic format see DOI:
1
0.1039/c4ra10808f
Fig. 1 The applications of tetrazines in the photonic materials and
‡
The authors Chen Li and Haixia Ge contributed equally to this work.
pharmacology.
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evaluated. We investigated the inuences of reaction tempera-
ture, amount of sulfur and reaction time on the yield of product.
Firstly, the CH CH OH was chosen as solvent. It is noteworthy
3
2
that ethanol is not only low cost and less toxic, but also more
efficient than other solvents. Then, different temperatures were
examined (entries 10, 13, 14) and 78 C was found to be the
Scheme 1 Preparation of 3,6-unsymmetrically disubstituted-1,2,4,5-
tetrazines from nitriles and hydrazine hydrate.
ꢀ
optimal temperature (entry 10). So the reaction temperature was
ꢀ
the boiling point of ethanol, 78 C. Moreover, the amount of
ꢀ
devoted our recent efforts to the design and synthesis of new sulfur was also investigated. At 78 C, the reaction of 1.0 equiv-
3
,6-unsymmetrically disubstituted-1,2,4,5-tetrazines, and the alent 1a and 2a, 10.0 equivalents 3 with 0.1 equivalent sulfur
investigation of their application potential.
resulted in only 27% of product 4a (Table 1, entry 3). When using
Herein, we detailed S-induced one-pot synthesis method for 1.0 equivalent sulfur, the yield was improved to 34% (Table 1,
target compounds, and 18 novel 3,6-unsymmetrically entry 4). When 4.0 equivalent sulfur were used, the yield of 4a was
disubstituted-1,2,4,5-tetrazines were rst reported (Scheme 1). increased to 72% (Table 1, entry 6). These results reveal that 4.0
23
Moreover, the spectral and electrochemical properties of equivalents sulfur are suitable for this reaction. The reaction
obtained compounds were examined. And a systematic theo- time was also tested. When the reaction time was increased to 12
retical investigation based on the density functional theory h, the product 4a was generated in 80% yield (Table 1, entry 10).
24
(
DFT) calculation were carried out. Amazingly, these 1,2,4,5- Thus, the optimal condition involved the following parameters:
ꢀ
tetrazines with the aromatic heterocyclic substituents at C3 and ethanol as a solvent, reaction temperature at 78 C, the amount
C6 positions not only can serve as special materials having both of sulfur as inducer, and the reaction time.
optical and electrochemical features, but also show the good
Under the optimized condition, additional aromatic nitriles
reactivity or selectivity in the inverse-type Diels–Alder reaction. were examined to expand the substrate scope, and the results
are summarized in Table 2. To our delight, the reaction of
various nitriles, such as cyanopyridine and substituted benzo-
Results and discussion
Synthesis
nitrile, with 3 underwent smoothly in excellent yields.
3a
On the basis of the related literature, a tentative mecha-
nism for the S-induced reaction between nitriles and hydrazine
hydrate, which synthesizes 3,6-unsymmetrically disubstituted-
As shown in Table 1, with 2-cyano-pyridine 1a (1.0 equivalent), 4-
methylbenzonitrile 2a (1.0 equivalent) and hydrazine hydrate 3
1,2,4,5-tetrazine derivatives via addition–elimination–rear-
(10 equivalents), the optimum reaction conditions for
rangement, was proposed in Scheme 2. To inducing the reac-
tion, the S is involved in the reaction process by reacting with
the synthesis of the corresponding 3-(pyridin-2-yl)-6-(p-tolyl)-
1,2,4,5-tetrazine 4a by an intermolecular cyclization were
3a
hydrazine hydrate to form NH
2
NHSH. The possible structure
of NH NHSH was calculated at DFT level using double-z basis
2
a
set (6-31G** for H element, 6-31+G* for S, N elements). Then,
Table 1 Optimizing reaction conditions
the NH NHSH interacts with nitrile to produce the key inter-
2
mediate [1], and this result is supported by the Fukui function
ꢁ
ꢁ
f
(r) calculation. The f(r) calculation result shows that the
nitrogen atom connecting with SH of the NH NHSH should be
the rst choice for the nitrile electrophilic attack since its value
2
ꢀ
b
Entry
T ( C)
Sulfur (equiv.)
t [h]
Yield (%) of condensed Fukui function (0.144) is larger than those of
ꢁ
other atoms. The 3D representation of Fukui function f(r) of
1
2
3
4
5
6
7
8
9
rt
0.05
0.05
0.1
1
2
4
4
4
4
4
9
9
9
9
9
9
5
7
10
12
14
12
12
12
12
17
20
27
34
59
72
55
63
76
80
81
0
ꢁ
NH NHSH and the condensed f
values of N atoms of
2
(r)
78
78
78
78
78
78
78
78
78
78
78
58
68
88
NH NHSH are shown in Scheme 2. The intermediate [1] further
2
reacts with the other nitrile to generate [2]. Then, the [2] might
be activated by eliminating of hydrogen sulde to form inter-
mediate [3]. Subsequently, the intermediate [3] converts to the
[4] by electrocyclic rearrangement. Finally, the intermediate [4]
converts to the target product by air oxidation. In the process of
reaction, symmetrical products are also generated, but their
yields are very low. The result may be arise from the fact that the
1
1
1
1
1
1
0
1
2
3
4
5
4
0
4
4
1
2
concentration of R -CN is much lower than that of R -CN aer
the intermediate [1] is produced. Then [1] more easily reacts
with the nitrile with a higher concentration to form the
unsymmetrical product. Thus the yield of the unsymmetrical
product is much higher than that of the symmetrical product.
Moreover, with a kind of nitrile as the substrate, the major
product is the symmetrical tetrazines.
64
73
79
4
a
Reaction condition: 1a, 2a (each 1.0 equivalent, 0.5 mmol), hydrazine
hydrate 3 (10.0 equivalents, 5.0 mmol), ethanol solution (3.0 mL), sulfur
ꢀ
b
(
4.0 equivalents, 2.0 mmol) at 78 C. Isolated product yields.
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Table 2 Synthesis of 3,6-unsymmetrically disubstituted-1,2,4,5-tetra-
a
zines (4a–v) induced by S under thermal conditions
Scheme 2 A tentative S-induced mechanism for synthesis of 3,6-
unsymmetrically disubstituted-1,2,4,5-tetrazine derivatives.
UV-vis spectroscopy
The UV-vis absorbance spectra of eight tetrazines 4d, 4e, 4f, 4p,
4
q, 4r, 4u, 4v in dichloromethane lie in the ultraviolet region,
and their absorption maxima are in the range of 270–346 nm
Fig. 2). Furthermore, these compounds all have an absorption
(
maximum in the region of 317–346 nm, which belongs to the
electron n–p* transition absorption band. For compounds 4v, a
shoulder peak can be observed around 300 nm. The maximum
absorption wavelengths (n–p* transition) of these compounds
show a certain variation regularity, which is 4d < 4e < 4f < 4u,
and 4p < 4q < 4r < 4v. The result reveals that the conjugated
degree increase can cause a red shi.
Fluorescence
Among all the compounds, we noticed that only 4d, 4e, 4f, 4p,
4q, 4r, 4u, and 4v can display uorescence, and their uores-
cence was shown in the visible region with the emission wave-
lengths lying in the range of 405–443 nm. And the uorescence
spectra and data of these compounds in dichloromethane are
shown in Fig. 3 and Table 3. Moreover, the uorescence
quantum yields (F
optically matching solutions of quinine sulfate (F
u
) of eight tetrazines were determined using
¼ 0.55 in
f
a
Reaction condition: nitriles (each 1.0 equivalent, 0.5 mmol), hydrazine
hydrate 3 (10.0 equivalents, 5.0 mmol), sulfur (4.0 equivalents, 2.0
mmol), ethanol solution (3.0 mL), at 78 C. Isolated product yields.
ꢀ
b
Fig. 2 UV-vis absorbance spectra of the compounds 4d, 4e, 4f, 4p,
ꢁ6
ꢁ1
4q, 4r, 4u, and 4v in dichloromethane (c ¼ 1 ꢂ 10 mol L ).
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respectively. The above results reveal that the substituents in
tetrazine and in phenyl rings both have the important effects on
the uorescence of these compounds. More importantly, the

uorescence of these compounds are in the visible range, sug-
gesting their good application potential as the photoelectricity
functional material and in photocatalyst technology.
Electrochemistry
Fig. 3 Fluorescence spectra of the compounds 4d, 4e, 4f, 4p, 4q, 4r,
ꢁ6
ꢁ1
4u, and 4v in dichloromethane (c ¼ 1 ꢂ 10 mol L ).
The synthesized tetrazines unsymmetrically substituted at C3
and C6 by the aromatic heterocycle are novel and interesting
compounds, which are different from those reported ones
ꢁ
1
(without substituents at C3 and C6 or substituted at C3 and C6
0.05 mol L
2 4
H SO ) as standards. The quantum yields were
by alkyl, specic substituent group methylthio, methoxy-
carbonyl, etc.) in terms of structure and properties. Especially,
the synthesized tetrazines are poor solubility and remain stable
in KOH environment, and this result is veried by experiment
test and structure analysis. For 4a–v, we have performed the
calculated according to the related ref. 25. It is noted that these
compounds with a uorescence have the common structural
character, which is the existence of an phenyl substituent (4-
XC
6
H
4
, X ¼ OCH
According to the phenyl substituent at C3, the eight
compounds can be divided into two series: (1) 4u, 4d, 4e, 4f
3 2
, NH ) at the C3 position.
26
electrochemical investigation, which is totally different from
the ones published in many closely related reports. Herein, the
electrochemical test was carried out in the beaker using three-
electrode system and CHI660B electrochemical workstation at
room temperature. The foam nickel previously prepared was
used as the working electrode. A platinum electrode and a
saturated calomel electrode (SCE) were used as the counter
electrode and the reference electrode, respectively. The typical
CV curves for the obtained samples in 2 M KOH electrolyte
(
–OCH
3
series) and (2) 4v, 4p, 4q, 4r (–NH
2
series). Comparison
OC ) and 4v (4-
of uorescence data of the 4u (4-CH
3
6
H
4
NH C H ) show that the uorescent wavelength of the latter is
2
6
4
longer, since the amino group possesses stronger electron-
donating ability resulting in bigger p-conjugation. Then, we
compared the uorescence data of –OCH series 4u, 4d, 4e, 4f,
3
and it is found that the uorescent wavelengths of 4d, 4e and 4f
are longer than that of 4u. Interestingly, this same situation
exists for –NH series compounds 4v, 4p, 4q and 4r. Further-
2
more, the observed change trends of uorescent wavelengths of
two series of compounds are 4f > 4d > 4e > 4u and 4r > 4q > 4p >
ꢁ
1
versus SCE at scan rate of 20 mV s were well dened and fully
reversible (Fig. 4).
Moreover, it is found that all the investigated tetrazines can
exhibit very high reduction potentials, and the electron-rich or
4v, respectively. This result could be explained by the intra-
molecular charge transfer (ICT). For 4d, 4e, 4f and 4p, 4q, 4r, the
whole molecule could form ICT from strong electron-donating
groups (4-XC
withdrawing group (strong electron-withdrawing group
N (pyridyl) or weaker electron-withdrawing groups (4-
Cl, Br)) in the C6 position, and thus the degree
6
H
4
, X ¼ OCH
3 2
, NH ) in C3 position to electron-
5 5
–C H
XC
6
H
4
, X ¼ CH
3
of p-conjugation is increased and the uorescent wavelengths
of these compounds are longer than those of 4u and 4v,
Table 3 Spectral data of compounds 4d, 4e, 4f, 4p, 4q, 4r, 4u, and 4v
in dichloromethane
a
b
Entry
lexc, max
lemi, max
F
u
4
4
4
4
4
4
4
4
d
e
f
u
p
q
r
335
335
335
335
344
344
344
344
407
405
418
396
430
441
443
408
0.54
0.35
0.67
0.10
0.22
0.58
0.37
0.43
v
a
The uorescence spectra of compounds 4d, 4e, 4f, 4p, 4q, 4r, 4u, and
v in dichloromethane (c ¼ 1 ꢂ 10 mol L ). The excitation slit width
b
ꢁ6
ꢁ1
4
is 1.5 nm, the emission slit width is 3 nm. Fluorescence quantum yield
Fig. 4 Cyclic voltammetry (CV) curves for compounds 4a–v, the
obtained samples in 2 M KOH electrolyte versus SCE at scan rate of 20
mV s , the voltage window was ranged from 0.0–0.5 V.
was determined by using quinine sulfate as a standard with F ¼ 0.55 in
ꢁ1
0
.05 mol L
H
2
SO
4
.
ꢁ1
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poor group in the heterocyclic substituent can cause a slightly local minimum due to the non-existence of imaginary
shi of the redox potential. For the reversible system, the frequency. Fukui function based on optimized structures has
equation as follows:
been calculated to determine the site reactivity and site
selectivity.
0
:059
DE
p
¼ Epa ꢁ Epc
¼
(1a)
(1b)
We systematically performed calculations for all the
synthesized tetrazine derivatives 4a–v. The geometry optimiza-
tion of 4a was based on its X-ray crystal structure (Fig. 5), and
the others were based on the molecular structures drawn by
Chem3D and Gaussview.
n
E
1/2 ¼ (Epa + Epc)/2
where Epa is the oxidation potential, Epc is the reduction
potential, DE is the potential difference between Epa and Epc
To investigate the site reactivity concerning nucleophilic
p
,
+
attack or site selectivity, the calculation of Fukui function f
(
r)
E1/2 is the half-wave potential, n is the electron transfer number.
The relevant electrochemical data are listed in Table 4. As
shown in Table 4, the highest reduction potential and half-wave
potential were displayed by 4f, and the lowest ones by 4e. For 4f,
the presence of 4-pyridine and 4-methoxylphenyl made the
tetrazine moiety highly electron-decient, and this facilitated
the reduction. Compounds 4a–v exhibited high reduction
potentials and half-wave potentials, which indicate that these
compounds all have the high charge storage ability. The above
results reveal that all compounds (4a–v) are potential function
materials with high electrochemical energy storage ability and
good electrocatalytic reduction effect.
28
for synthesized tetrazines was carried out. The equation of
+
Fukui function f(r) as follows:
0
1
ꢀ ꢁ
ꢂ
ꢃ
vr ~r
ꢀ ꢁ
ꢀ ꢁ
þ
¼ @
A ¼ r ~r
f
ðrÞ
ꢁ r ~r N
(2a)
(2b)
Nþ1
vN
n
n
+
N+1
N
f(r) ¼ qx
ꢁ qx
where N is the number of electrons, n is dened as the external
x
potential, q is the electronic population of atom x in a
molecule.
For 4a, the 3D representation of the Fukui function and the
condensed Fukui function of atoms are shown in Fig. 6 (4b–v,
see in the ESI†). The 3D representation of f(r) clearly demon-
strates that the region around the N atoms of the 1,2,4,5-tetra-
zine skeleton possess higher reactivity than other parts.
Therefore the 1,2,4,5-tetrazine skeleton as the electron-decient
unit may has the stronger electrophilic ability, and can be used
as the 4-p components in the inverse-type Diels–Alder reaction.
Theoretical study
+
All the calculations were carried out with the Gaussian 09
27
program package using the hybrid density functional theory
B3LYP) method. Basis sets of double-z quality (6-31G** for C, H
(
atoms, 6-31+G* for other atoms) were used for the geometry
optimization. The optimized structures were conrmed to be
a
Table 4 Potential (in V vs. SCE) of the compounds 4a–v
Entry
E
pa
E
pc
DE
p
E
1/2
n
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
0.357
0.332
0.347
0.389
0.330
0.396
0.352
0.340
0.349
0.383
0.328
0.384
0.369
0.327
0.393
0.370
0.327
0.355
0.343
0.350
0.352
0.355
0.265
0.236
0.258
0.309
0.235
0.314
0.261
0.270
0.260
0.294
0.240
0.302
0.307
0.240
0.304
0.260
0.263
0.260
0.243
0.265
0.261
0.263
0.092
0.097
0.089
0.080
0.094
0.082
0.091
0.070
0.089
0.089
0.088
0.082
0.062
0.087
0.089
0.110
0.064
0.095
0.100
0.085
0.091
0.092
0.311
0.284
0.303
0.349
0.283
0.355
0.307
0.305
0.305
0.316
0.284
0.343
0.338
0.284
0.349
0.315
0.295
0.306
0.293
0.308
0.307
0.309
0.64
0.61
0.66
0.74
0.63
0.72
0.65
0.84
0.66
0.66
0.67
0.72
0.95
0.68
0.66
0.54
0.92
0.62
0.59
0.69
0.65
0.64
Fig. 5 X-ray crystal structure of 4a.
s
t
u
v
+
a
Fig. 6 3D representation of the Fukui function f(r) (positive in red
E
pa represents the oxidation potential; Epc represents the reduction
potential; DE
p
is the potential difference between Epa and Epc; E1/2 is color and negative in green color) and the condensed Fukui function
+
the half-wave potential; n is the number of electron transferred.
f(r) of related atoms of 4a.
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+
Furthermore, the f(r) calculation results also indicate the in Fig. 7 (the shapes of HOMO and LUMO orbitals of 4b–v are
regioselectivity in the inverse-type Diels–Alder reaction. shown in the ESI†). The energies of HOMO, LUMO, and the
The frontier orbitals HOMO and LUMO for all the synthe- LUMO–HOMO gap for 4a–v are depicted in Table 5.
sized tetrazine derivatives have been also calculated. The 3D The inverse-type Diels–Alder reactions between 1,2,4,5-tet-
representations of HOMO and LUMO orbitals of 4a are shown razines and electron-rich dienes depends on the LUMOdiene
–
29
HOMOdienophile gap. Thus for these 1,2,4,5-tetrazine deriva-
tives as the electron-decient dienophile, elevating their HOMO
energies can facilitate the reaction. We compared the energies
of HOMO, LUMO, and the LUMO–HOMO gap for 4a–v, the
result reveals that using NH , CH O, and CH as substituent can
2
3
3
increase the HOMO energies in comparison to the CN and CF3,
that is to say, the electron-donating substituents will increase
the HOMO energies of these compounds. Moreover, we inves-
tigated the frontier molecular orbitals (FMOs) of previously
reported 3,6-disubstituted-1,2,4,5-tetrazines, which have the
11d,11f,34
good reactivity in the inverse-type Diels–Alder reaction.
The HOMO energies of our tetrazine derivatives are comparable
to those of the reported tetrazine derivatives, and some of them
even have the higher HOMO energies than the reported ones
(Table 5). Therefore, almost all of the compounds (4a–v) have
the good potential of participating in the inverse-type Diels–
Fig. 7 3D representations of HOMO and LUMO orbitals of 4a.
Alder reaction.
a
Table 5 Calculated frontier orbitals energies (eV) for 4a–v
Conclusions
Entry
E
HOMO
E
LUMO
DEL–H
In conclusion, tetrazines unsymmetrically substituted at C3 and
C6 positions by aromatic heterocyclic groups have been sys-
tematacially synthesized, and 18 novel 3,6-unsymmetrically
disubstituted-1,2,4,5-tetrazines have been reported for the rst
time. The spectral and electrochemical properties of these
synthesized tetrazines have also been investigated. These
synthesized tetrazine derivatives display the intense uores-
cence and fully reversible electrochemical behaviors, and the
result indicate the good potential of these compounds in
photonic applications. And it is found that the substituents
both in tetrazine and in phenyl rings have the important effects
on their spectral and electrochemical properties. In addition,
the DFT calculations suggest that these synthesized tetrazines,
as the electron-decient dienophile, can exert the good reaction
reactivity or selectivity in the inverse electron demand Diels–
Alder reaction. The above results indicates that these 3,6-
unsymmetrically disubstituted-1,2,4,5-tetrazine derivatives
have the large potential to be the good lead compounds that can
be used in many elds. Moreover, the further investigation of
these tetrazine derivatives is warranted for developing their
applications.
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
ꢁ6.265
ꢁ6.455
ꢁ6.569
ꢁ6.208
ꢁ6.299
ꢁ6.406
ꢁ6.643
ꢁ6.832
ꢁ6.957
ꢁ6.491
ꢁ6.681
ꢁ6.800
ꢁ6.501
ꢁ6.691
ꢁ6.810
ꢁ5.717
ꢁ5.876
ꢁ5.882
ꢁ6.723
ꢁ6.973
ꢁ5.881
ꢁ5.435
ꢁ2.746
ꢁ2.980
ꢁ3.063
ꢁ2.691
ꢁ2.926
ꢁ3.004
ꢁ3.131
ꢁ3.356
ꢁ3.445
ꢁ2.978
ꢁ3.205
ꢁ3.290
ꢁ2.988
ꢁ3.214
ꢁ3.299
ꢁ2.545
ꢁ2.752
ꢁ2.762
ꢁ3.271
ꢁ3.453
ꢁ2.618
ꢁ2.404
3.52
3.48
3.51
3.52
3.37
3.40
3.51
3.48
3.51
3.51
3.48
3.51
3.51
3.48
3.51
3.17
3.12
3.12
3.45
3.52
3.26
3.03
s
t
u
v
ꢁ
ꢁ
ꢁ
6.324
8.154
6.630
ꢁ2.832
ꢁ4.519
ꢁ3.095
3.49
3.64
3.54
Experimental
General remarks
1
13
H NMR (400 MHz), C NMR (100 MHz) spectra were recorded
1
on 400 MHz spectrometers. Chemical shis for H NMR spectra
are reported in parts per million downeld from TMS, chemical
shis for C NMR spectra are reported in ppm relative to
internal chloroform. Infrared spectra (IR) were recorded with
KBr pellets. Silica gel (200–300 mesh) was used for column
chromatography. High-resolution mass spectra were obtained
ꢁ
6.337
ꢁ2.803
3.53
1
3
a
EHOMO, ELUMO, DEL–H represent the energies of HOMO, LUMO, and the
LUMO–HOMO gap, respectively.
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using ESI. The UV-vis absorption spectra, uorescence spectra 3-(4-Methoxyphenyl)-6-(pyridin-2-yl)-1,2,4,5-tetrazine (4d)
were recorded in dichloromethane as solvent on a UV-2520
Silica gel chromatography (petroleum ether–ethyl acetate ¼
spectrophotometer, RF-5301 PC uorescence spectrophoto-
meter, respectively. The single-crystal structure of 4a was
determined by X-ray crystallography (ESI†).
ꢀ
1
2
: 1, R
f
¼ 0.18); white solid (106.0 mg, 80%); mp: >270 C; H
NMR (400 MHz, CDCl
3
) d 8.70 (d, J ¼ 4.4 Hz, 1H), 8.41 (d, J ¼ 8.0
Hz, 1H), 7.99 (d, J ¼ 8.5 Hz, 2H), 7.88 (t, J ¼ 7.7 Hz, 1H), 7.40 (dd,
J ¼ 12.4, 6.4 Hz, 1H), 7.02 (d, J ¼ 8.4 Hz, 2H), 3.89 (s, 3H) ppm;
General procedure for the S-induced the reaction of nitriles
and hydrazine hydrate
13
3
C NMR (100 MHz, CDCl ) d 172.2, 150.3, 150.1, 149.7, 137.4,
1
29.9, 125.7, 121.3, 121.2, 114.9, 100.3, 55.8 ppm; IR(KBr) nmax/
ꢁ
1
To a round-bottom ask, two kinds of nitriles (each 0.5 mmol), cm 1606, 1517, 1437, 1408, 1307, 1249, 1173, 1115, 1029, 985,
sulfur (64 mg, 2.0 mmol) were added to an ethanol solution (3.0 828, 601; HRMS (ESI) m/z: [M + Na] calcd for C14
+
+
H N O + Na
11 5
mL). Then hydrazine hydrate (250 mg, 5.0 mmol) was added in 288.0861; found: 288.0827.
drops into the solution. The mixture was stirred overnight at the
required reaction temperature. The reaction was monitored by 3-(4-Methoxyphenyl)-6-(pyridin-3-yl)-1,2,4,5-tetrazine (4e)
TLC. Aer completion, the mixture was cooled, dichloro-
Silica gel chromatography (petroleum ether–ethyl acetate ¼
methane (8 mL) and water (5 mL) were added, and the sulfur
was separated by the ltration. Aer the extraction with
dichloromethane, the separated organic layer was dried over
ꢀ
2
: 1, R ¼ 0.23); white solid (107.4 mg, 81%); mp: 158–159 C;
f
1
H NMR (400 MHz, CDCl
3
) d 9.17 (s, 1H), 8.73 (d, J ¼ 4.2 Hz, 1H),
8
4
.37 (d, J ¼ 7.9 Hz, 1H), 7.97 (d, J ¼ 8.7 Hz, 2H), 7.46 (dd, J ¼ 7.8,
CaCl
2
, and concentrated under reduced pressure. The crude
13
.9 Hz, 1H), 7.02 (d, J ¼ 8.7 Hz, 2H), 3.89 (s, 3H) ppm; C NMR
residue was puried by ash chromatography on silica gel using
petroleum ether/ethyl acetate as eluent to afford the desired
product.
(100 MHz, CDCl
3
) d 168.4, 163.7, 162.0, 151.4, 148.6, 134.5,
ꢁ1
1
29.5, 126.5, 123.8, 122.2, 114.5, 55.3 ppm; IR (KBr) nmax/cm
1607, 1571, 1403, 1250, 1178, 1026, 835, 705.
3-(Pyridin-2-yl)-6-(p-tolyl)-1,2,4,5-tetrazine (4a)
3-(4-Methoxyphenyl)-6-(pyridin-4-yl)-1,2,4,5-tetrazine (4f)
Silica gel chromatography (petroleum ether–ethyl acetate ¼
Silica gel chromatography (petroleum ether–ethyl acetate ¼
2
: 1, R
f
¼ 0.26); purple solid (99.6 mg, 80% yield); mp: 178–181
) d 8.97 (d, J ¼ 3.4 Hz, 1H), 8.70 (d,
ꢀ
2
: 1, R
f
¼ 0.22); white solid (104.7 mg, 79%); mp: 164–165 C;
ꢀ
1
1
C; H NMR (400 MHz, CDCl
3
H NMR (400 MHz, CDCl ) d 8.77 (d, J ¼ 5.0 Hz, 2H), 7.97 (d, J ¼
3
J ¼ 7.9 Hz, 1H), 8.60 (d, J ¼ 8.0 Hz, 2H), 8.00 (t, J ¼ 7.1 Hz, 1H),
8
.6 Hz, 2H), 7.86 (d, J ¼ 5.0 Hz, 2H), 7.02 (d, J ¼ 8.6 Hz, 2H), 3.89
1
3
13
7
.62–7.53 (m, 1H), 7.44 (d, J ¼ 7.9 Hz, 2H), 2.50 (s, 3H) ppm;
C
(s, 3H) ppm; C NMR (100 MHz, CDCl ) d 169.1, 164.6, 162.1,
3
3
NMR (100 MHz, CDCl ) d 164.6, 163.5, 151.1, 150.6, 144.1, 137.7,
30.4, 129.0, 128.6, 126.5, 124.0, 22.0 ppm; IR (KBr) nmax/cm
605, 1580, 1393, 1245, 1177, 1116, 919, 812; HRMS (ESI) m/z:
1
50.6, 137.1, 129.5, 122.1, 121.3, 114.5, 55.4 ppm; IR(KBr) nmax/
ꢁ
1
ꢁ
1
+
1
1
cm 1598, 1400, 1313, 1179, 824, 698; HRMS (ESI) m/z: [M + H]
calcd for C14H N O + H 266.1042; found: 266.1049.
11 5
+
+
+
[M + Na] calcd for C14
11 5
H N + Na 250.1093; found: 250.1093.
3-(Pyridin-2-yl)-6-(4-(triuoromethyl)phenyl)-1,2,4,5-tetrazine
3-(Pyridin-3-yl)-6-(p-tolyl)-1,2,4,5-tetrazine (4b)
(4g)
Silica gel chromatography (petroleum ether–ethyl acetate ¼ Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
1
2
: 1, R
f
¼ 0.40); purple solid (100.9 mg, 81%); mp: 197–199 C; 2 : 1, R ¼ 0.25); purple solid (115.2 mg, 76%); H NMR (400
f
1
H NMR (400 MHz, CDCl
3
) d 9.85 (s, 1H), 8.88 (dd, J ¼ 6.6, 5.3 MHz, CDCl ) d 9.00 (d, J ¼ 4.2 Hz, 1H), 8.84 (d, J ¼ 8.0 Hz, 2H),
3
Hz, 2H), 8.54 (dd, J ¼ 8.2, 5.3 Hz, 2H), 7.77 (d, J ¼ 8.5 Hz, 1H), 8.73 (d, J ¼ 7.8 Hz, 1H), 8.03 (t, J ¼ 7.7 Hz, 1H), 7.90 (d, J ¼ 8.0
1
3
13
7.55–7.59 (m, 1H), 7.43 (d, J ¼ 8.0 Hz, 1H), 2.49 (s, 3H) ppm;
C
Hz, 2H), 7.60 (t, 1H) ppm; C NMR (100 MHz, CDCl ) d 163.6,
3
NMR (100 MHz, CDCl ) d 164.6, 162.9, 153.3, 149.4, 144.2, 135.1, 163.4, 150.9, 149.8, 137.4, 134.7, 134.5, 128.5, 126.5, 126.2,
30.4, 128.9, 128.4, 128.2, 124.2, 22.0 ppm; IR (KBr) nmax/cm
361, 1604, 1583, 1393, 1178, 1107, 1017, 917, 849, 817, 593; 1113, 1067, 910, 825; HRMS (ESI) m/z: [M + H] calcd for
11 5
14 8 3 5
HRMS (ESI) m/z: [M + Na] calcd for C14H N + Na 250.1093; C H F N + H 304.0810; found: 304.0809.
3
ꢁ
1
ꢁ1
1
2
126.1, 124.1 ppm; IR(KBr) nmax/cm 1581, 1398, 1327, 1156,
+
+
+
+
found: 250.1093.
3-(Pyridin-3-yl)-6-(4-(triuoromethyl)phenyl)-1,2,4,5-tetrazine
3-(Pyridin-4-yl)-6-(p-tolyl)-1,2,4,5-tetrazine (4c)
(4h)
Silica gel chromatography (petroleum ether–ethyl acetate ¼ Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
1
2
: 1, R
f
¼ 0.39); purple solid (103.4 mg, 83%), mp: 231–233 C; 2 : 1, R
f
¼ 0.29); purple solid (113.7 mg, 75%); H NMR (400
1
H NMR (400 MHz, CDCl
8
(
3
) d 8.92 (d, J ¼ 5.9 Hz, 2H), 8.56 (d, J ¼ MHz, CDCl ) d 9.89 (s, J ¼ 1.6 Hz, 1H), 8.93 (dq, J ¼ 4.8, 1.6 Hz,
3
.2 Hz, 2H), 8.47 (d, J ¼ 6.0 Hz, 2H), 7.43 (d, J ¼ 8.1 Hz, 2H), 2.50 2H), 8.81 (d, J ¼ 8.2 Hz, 2H), 7.91 (d, J ¼ 8.3 Hz, 2H), 7.60 (dd, J ¼
1
3
1
3
s, 3H) ppm; C NMR (100 MHz, CDCl ) d 164.6, 162.6, 151.0, 7.9, 4.9 Hz, 1H) ppm; C NMR (100 MHz, CDCl ) d 187.6, 163.5,
3
3
1
44.2, 139.2, 130.2, 128.4, 128.3, 121.0, 21.7 ppm; IR(KBr) nmax/ 163.2, 153.5, 149.4, 135.2, 134.7, 128.4, 127.5, 126.3, 126.3, 124.0
ꢁ
1
ꢁ1
cm 2914, 1604, 1595, 1393, 1212, 1179, 1054, 921, 828, 598; ppm; IR(KBr) nmax/cm 1587, 1517, 1394, 1321, 1193, 1162,
HRMS (ESI) m/z: [M + Na] calcd for C14
found: 250.1093.
+
+
+
H
11
N
5
+ Na 250.1093; 1114, 1067, 909, 863, 830; HRMS (ESI) m/z: [M + H] calcd for
+
14 8 3 5
C H F N + H 304.0810; found: 304.0817.
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3-(Pyridin-4-yl)-6-(4-(triuoromethyl)phenyl)-1,2,4,5-tetrazine
3-(4-Bromophenyl)-6-(pyridin-3-yl)-1,2,4,5-tetrazine (4n)
(
4i)
Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
Silica gel chromatography (petroleum ether–ethyl acetate ¼ 2 : 1, R
f
¼ 0.27); purple solid (112.7 mg, 72%); mp: 229–231 C;
1
1
2
: 1, R
f
¼ 0.28); purple solid (118.2 mg, 78%); H NMR (400
3
H NMR (400 MHz, CDCl ) d 9.87 (s, 1H), 8.89–8.92 (m, 2H), 8.55
MHz, CDCl
8
3
) d 8.96 (d, J ¼ 4.5 Hz, 2H), 8.83 (d, J ¼ 8.1 Hz, 2H), (d, J ¼ 8.6 Hz, 2H), 7.79 (d, J ¼ 8.6 Hz, 2H), 7.58 (dd, J ¼ 7.9, 4.9
13 13
.51 (d, J ¼ 4.5 Hz, 2H), 7.92 (d, J ¼ 8.2 Hz, 2H) ppm; C NMR Hz, 1H) ppm; C NMR (100 MHz, CDCl
3
) d 164.0, 163.1, 153.4,
(100 MHz, CDCl ) d 163.8, 163.2, 151.2, 138.8, 134.8, 134.5, 149.4, 135.1, 132.8, 130.4, 129.6, 128.4, 127.8, 124.1 ppm;
3
ꢁ
1
ꢁ1
1
1
28.6, 126.4, 126.4, 121.3 ppm; IR(KBr) nmax/cm 1633, 1400, IR(KBr) nmax/cm 1635, 1588, 1400, 1109, 914, 820, 590; HRMS
325, 1170, 1132, 1067, 1108, 918, 841; HRMS (ESI) m/z: [M + H]
+
+
+
(ESI) m/z: [M + H] calcd for C H BrN + H 314.0041; found:
13 8 5
+
calcd for C H F N + H 304.0810; found: 304.0805.
314.0036.
-(4-Bromophenyl)-6-(pyridin-4-yl)-1,2,4,5-tetrazine (4o)
1
4
8 3 5
3
3
-(4-Chlorophenyl)-6-(pyridin-2-yl)-1,2,4,5-tetrazine (4j)
Silica gel chromatography (petroleum ether–ethyl acetate ¼
Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
2
: 1, R ¼ 0.28); purple solid (115.8 mg, 74%); mp: 244–247 C;
f
ꢀ
1
2
: 1, R ¼ 0.27); purple solid (99.5 mg, 74%); mp: 218–219 C; H
1
f
H NMR (400 MHz, CDCl ) d 8.95 (d, J ¼ 5.8 Hz, 2H), 8.57 (d, J ¼
3
NMR (400 MHz, CDCl ) d 8.98 (d, J ¼ 4.6 Hz, 1H), 8.70 (d, J ¼ 7.9
3
8
.6 Hz, 2H), 8.50 (d, J ¼ 5.9 Hz, 2H), 7.80 (d, J ¼ 8.6 Hz, 2H) ppm;
Hz, 1H), 8.66 (d, J ¼ 8.5 Hz, 2H), 8.01 (t, J ¼ 7.7 Hz, 1H), 7.66– 13
C NMR (100 MHz, CDCl
3
) d 164.3, 163.0, 151.2, 139.0, 132.9,
1
3
7
1
.55 (m, 3H) ppm; C NMR (100 MHz, CDCl
51.2, 150.4, 139.9, 137.7, 130.2, 130.0, 129.9, 126.7, 124.2 ppm;
3
) d 164.0, 163.7,
ꢁ1
1
1
30.2, 129.7, 128.7, 121.2 ppm; IR(KBr) nmax/cm 1638, 1584,
396, 1173, 1106, 1005, 920, 831, 593; HRMS (ESI) m/z: [M + H]
+
ꢁ
1
IR(KBr) nmax/cm 2361, 1633, 1588, 1394, 1118, 1085, 913, 813;
HRMS (ESI) m/z: [M + H] calcd for C13
+
calcd for C13
H
8
BrN
5
+ H 314.004; found: 314.0048.
+
+
H
8
ClN
5
+ H 270.0546;
found: 270.0544.
4-(6-(p-Tolyl)-1,2,4,5-tetrazin-3-yl)aniline (4p)
Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
3
-(4-Chlorophenyl)-6-(pyridin-3-yl)-1,2,4,5-tetrazine (4k)
3 : 1, R ¼ 0.32); yellow solid (110.5 mg, 85%); mp: 180–181 C;
f
1
H NMR (400 MHz, CDCl3) d 7.88 (d, J ¼ 7.8 Hz, 2H), 7.81 (d, J ¼
Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
8.1 Hz, 2H), 7.28 (d, J ¼ 12.7 Hz, 2H), 6.74 (d, J ¼ 8.1 Hz, 2H),
2
: 1, R
f
¼ 0.28); purple solid (100.9 mg, 75%); mp: 217–219 C;
1
3
1
4.01 (s, 2H), 2.42 (s, 3H) ppm; C NMR (100 MHz, CDCl ) d
3
H NMR (400 MHz, CDCl
3
) d 9.86 (s, 1H), 8.90 (t, J ¼ 6.8 Hz, 2H),
13
168.4, 166.9, 149.4, 141.4, 130.0, 129.6, 127.9, 120.5, 115.1, 21.7
8
.63 (d, J ¼ 8.5 Hz, 2H), 7.57–7.63 (m, 3H) ppm; C NMR (100
ꢁ
1
ppm; IR(KBr) nmax/cm 3130, 1600, 1516, 1401, 1261, 1098,
MHz, CDCl ) d 163.9, 163.1, 153.5, 149.5, 139.9, 135.3, 130.1,
3
ꢁ
1
1019, 825.
1
1
30.0, 129.6, 127.9, 124.2 ppm; IR(KBr) nmax/cm 1638, 1589,
+
407, 1172, 1098, 912, 820; HRMS (ESI) m/z: [M + H] calcd for
+
C
13
H
8
ClN
5
+ H 270.0546; found: 270.0547.
4-(6-(4-Chlorophenyl)-1,2,4,5-tetrazin-3-yl)aniline (4q)
Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
3
: 1, R ¼ 0.31); yellow solid (111.8 mg, 79%); mp: 192–194 C;
f
3
-(4-Chlorophenyl)-6-(pyridin-4-yl)-1,2,4,5-tetrazine (4l)
1
H NMR (400 MHz, CDCl
3
) d 7.93 (d, J ¼ 8.5 Hz, 2H), 7.81 (d, J ¼
Silica gel chromatography (petroleum ether–ethyl acetate ¼ 8.5 Hz, 2H), 7.46 (d, J ¼ 8.5 Hz, 2H), 6.74 (d, J ¼ 8.5 Hz, 2H), 4.04
ꢀ
1
13
2
: 1, R ¼ 0.28); purple solid (98.2 mg, 73%); mp: 242–243 C; H (s, 2H) ppm; C NMR (100 MHz, CDCl ) d 168.7, 165.2, 149.3,
f
3
NMR (400 MHz, CDCl ) d 8.94 (d, J ¼ 4.5 Hz, 2H), 8.64 (d, J ¼ 8.0 136.7, 129.5, 129.3, 128.9, 128.8, 120.0, 114.8 ppm; IR(KBr) nmax/
3
ꢁ
1
Hz, 2H), 8.49 (d, J ¼ 4.5 Hz, 2H), 7.63 (d, J ¼ 8.1 Hz, 2H) ppm; cm 3133, 1629, 1400, 1181, 1089, 821.
1
3
C NMR (100 MHz, CDCl
39.41, 130.28, 130.00, 121.58, 100.38 ppm; IR(KBr) nmax/cm
635, 1592, 1400, 1170, 1091, 1007, 915, 830; HRMS (ESI) m/z:
3
) d 164.49, 163.36, 151.60, 140.41,
ꢁ
1
1
1
4
-(6-(4-Bromophenyl)-1,2,4,5-tetrazin-3-yl)aniline (4r)
+
+
Silica gel chromatography (petroleum ether–ethyl acetate ¼
8 5
[M + H] calcd for C13H ClN + H 270.0546; found: 270.0544.
ꢀ
3
: 1, R
f
¼ 0.34); yellow solid (132.4 mg, 81%); mp: 236–238 C;
1
H NMR (400 MHz, CDCl
3
) d 7.86 (d, J ¼ 8.2 Hz, 2H), 7.81 (d, J ¼
8
(
1
.3 Hz, 2H), 7.62 (d, J ¼ 8.0 Hz, 2H), 6.74 (d, J ¼ 8.1 Hz, 2H), 4.04
3-(4-Bromophenyl)-6-(pyridin-2-yl)-1,2,4,5-tetrazine (4m)
1
3
s, 2H) ppm; C NMR (100 MHz, DMSO) d 174.0, 169.0, 157.3,
Silica gel chromatography (petroleum ether–ethyl acetate ¼
37.5, 134.3, 134.3, 134.2, 129.3, 121.4, 118.8 ppm; IR(KBr) nmax/
ꢀ
2
: 1, R
f
¼ 0.28); purple solid (117.4 mg, 75%); mp: 191–193 C;
ꢁ
1
cm 3131, 1627, 1521, 1401, 1178, 1129, 986, 823.
1
H NMR (400 MHz, CDCl
3
) d 8.98 (d, J ¼ 4.3 Hz, 1H), 8.70 (d, J ¼
7
.9 Hz, 1H), 8.57 (d, J ¼ 8.3 Hz, 2H), 8.01 (t, J ¼ 7.7 Hz, 1H), 7.77
30
1
3
3,6-Di(pyridin-3-yl)-1,2,4,5-tetrazine (4s)
(d, J ¼ 8.3 Hz, 2H), 7.58 (dd, J ¼ 7.4, 4.8 Hz, 1H) ppm; C NMR
(
100 MHz, CDCl ) d 164.1, 163.7, 151.2, 150.3, 137.7, 132.9, Silica gel chromatography (methanol–dichloromethane
¼
3
ꢁ
1
ꢀ
1
1
30.6, 129.9, 128.5, 126.7, 124.2 ppm; IR(KBr) nmax/cm 1584, 1 : 20, R ¼ 0.40); purple solid (96.8 mg, 82%); mp: 203–204 C;
f
+
1
393, 1116, 1066, 913, 862, 588; HRMS (ESI) m/z: [M + H] calcd
H NMR (400 MHz, CDCl
3
) d 9.86 (s, 2H), 8.90 (t, J ¼ 6.6 Hz, 4H),
+
13
for C13
H
8
BrN
5
+ H 314.0041; found: 314.0029.
7.57 (dd, J ¼ 7.8, 5.0 Hz, 2H) ppm; C NMR (100 MHz, CDCl
3
) d
12284 | RSC Adv., 2015, 5, 12277–12286
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ꢁ1
1
1
63.6, 153.7, 149.6, 135.4, 127.8, 124.3 ppm; IR(KBr) nmax/cm
584, 1387, 1126, 1016, 917, 821, 704, 598.
2 S. Jaiswal, P. C. Varma, L. O'Neill, B. Duffy and P. McHale,
Mater. Sci. Eng., C, 2013, 33, 1925.
3
(a) P. Audebert, S. Sadki, F. Miomandre, G. Clavier,
31
`
M. C. Vernieres, M. Saoud and P. Hapiot, New J. Chem.,
3
,6-Di(pyridin-4-yl)-1,2,4,5-tetrazine (4t)
2
004, 28, 387; (b) P. Audebert, F. Miomandre, G. Clavier,
Silica gel chromatography (methanol–dichloromethane
1
¼
1
M. Verni `e res, S. Badr ´e and R. M ´e allet-Renault, Chem.–Eur.
J., 2005, 11, 5667; (c) C. Dumas-Verdes, F. Miomandre,
E. L ´e picier, O. Galangau, T. Vu, G. Clavier, R. M ´e allet-
Renault and P. Audebert, Eur. J. Org. Chem., 2010, 2525; (d)
N. K. Devaraj, S. Hilderbrand, R. Upadhyay, R. Mazitschek
and R. Weissleder, Angew. Chem., 2010, 122, 293; (e) Z. Li,
J. Ding, N. Song, X. Du, J. Zhou, J. Lu and Y. Tao, Chem.
Mater., 2011, 23, 1977; (f) Q. Zhou, P. Audebert, G. Clavier,
R. M ´e allet-Renault, F. Miomandre, Z. Shaukat, T. Vu and
J. Tang, J. Phys. Chem. C, 2011, 115, 21899.
ꢀ
: 20, R
f
¼ 0.40); purple solid (98.0 mg, 83%); mp: >200 C; H
NMR (400 MHz, CDCl ) d 8.97 (d, J ¼ 4.9 Hz, 4H), 8.53 (d, J ¼ 4.9
3
1
3
Hz, 4H) ppm; C NMR (100 MHz, CDCl ) d 163.7, 151.3, 138.6,
3
ꢁ1
121.4 ppm; IR(KBr) nmax/cm 2361, 1588, 1557, 1411, 1389,
1261, 1110, 1053, 921, 831, 715, 600.
32
3,6-Bis(4-methoxyphenyl)-1,2,4,5-tetrazine (4u)
Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
3
: 1, R ¼ 0.27); white solid (113.2 mg, 77%); mp: 170–171 C;
f
1
H NMR (400 MHz, CDCl
3
) d 7.93 (d, J ¼ 8.8 Hz, 4H), 7.00 (d, J ¼
4 (a) N. K. Devaraj, R. Weissleder and S. A. Hilderbrand,
Bioconjugate Chem., 2008, 19, 2297–2299; (b)
1
3
8
1
2
3
.8 Hz, 4H), 3.88 (s, 6H) ppm; C NMR (100 MHz, CDCl ) d
67.0, 161.7, 129.3, 122.9, 114.4, 55.4 ppm; IR(KBr) nmax/cm
361, 1608, 1401, 1250, 1173, 987, 828.
ꢁ
1
M. L. Blackman, M. Royzen and J. M. Fox, J. Am. Chem.
Soc., 2008, 130, 13518; (c) D. S. Liu, A. Tangpeerachaikul,
R. Selvaraj, M. T. Taylor, J. M. Fox and A. Y. Ting, J. Am.
Chem. Soc., 2012, 134, 792; (d) J. Lub, W. Ten Hoeve,
R. Rossin, S. M. Van Den Boschg and M. S. Robillard, WO
patent, 2012049624, 2012.
0
,4 -(1,2,4,5-Tetrazine-3,6-diyl)dianiline (4v)
33
4
Silica gel chromatography (petroleum ether–ethyl acetate ¼
ꢀ
1
1
: 1, R
f
¼ 0.20); yellow solid (93.8 mg, 71%); mp: >280 C; H
5
Y. Zhao, Y. Li, Z. Qin, R. Jiang, H. Liu and Y. Li, Dalton Trans.,
2012, 41, 13338.
NMR (400 MHz, DMSO) d 7.62 (d, J ¼ 7.4 Hz, 4H), 6.66 (d, J ¼ 7.5
1
3
Hz, 4H), 5.82 (s, 4H) ppm; C NMR (100 MHz, DMSO) d 171.2,
ꢁ
1
6 (a) G. Clavier and P. Audebert, Chem. Rev., 2010, 110, 3299;
b) J. Malinge, C. Allain, A. Brosseau and P. Audebert,
1
1
56.7, 133.9, 122.1, 118.8 ppm; IR(KBr) nmax/cm 3126, 1627,
(
903, 1400, 1307, 1178, 831, 776.
Angew. Chem., 2012, 124, 8662; (c) C. Quinton, V. Alain-
Rizzo, C. Dumas-Verdes, G. Clavier, F. Miomandre and
P. Audebert, Eur. J. Org. Chem., 2012, 1394.
General procedure for preparation of solid electrode loaded
test samples for electrochemical testing
7
(a) N. K. Devaraj, S. Hilderbrand, R. Upadhyay, R. Mazitschek
The synthesized powder sample was mixed with acetylene black
and caking agent polyvinylidene uoride (PVDF) in certain
proportion, and a suitable amount of anhydrous CH CH OH as
and R. Weissleder, Angew. Chem., 2010, 122, 2931; (b)
C. M. Cole, J. Yang, J. ˇS e ˇc kut ˙e and N. K. Devaraj,
ChemBioChem, 2013, 14, 205.
3
2
demulsier was added. And the mixture was grinded into a
paste in the agate mortar, then it was besmeared on the nickel
foam sheet several times (1 cm ꢂ 1.5 cm). At last, the nickel
8 Z. Li, J. Ding, N. Song, J. Lu and Y. Tao, J. Am. Chem. Soc.,
2010, 132, 13160.
9 (a) D. E. Chavez and M. A. Hiskey, J. Energ. Mater., 1999, 17,
357; (b) P. F. Pagoria, G. S. Lee, A. R. Mitchell and
R. D. Schmidt, Thermochim. Acta, 2002, 384, 187; (c)
D. E. Chavez, M. A. Hiskey and R. D. Gilardi, Org. Lett.,
ꢀ
foam sheet was dried at 60 C for 24 h and compressed with a
compression stress of 10 MPa.
2
004, 6, 2889; (d) T. Wei, W. Zhu, X. Zhang, Y. F. Li and
Acknowledgements
H. Xiao, J. Phys. Chem. A, 2009, 113, 9404; (e) A. Saikia,
R. Sivabalan, B. G. Polke, G. M. Gore, A. Singh,
A. Subhananda Rao and A. K. Sikder, J. Hazard. Mater.,
2009, 170, 306.
The project was supported by the National Natural Science
Foundation of China (NSFC 21272184; 20972124; 21143010;
21103137), the Shaanxi Provincial Natural Science Fund Project
(no. 2012JQ2007), the Northwest University Science Foundation 10 (a) D. E. Chavez, M. A. Hiskey and R. D. Gilardi, Angew.
for Postgraduate Students (no. YZZ13042), the Xi'an City Science
and Technology Project [no. CXY1429(6); CXY1434(7)], and the
Chinese National Innovation Experiment Program for Univer-
sity Students (no. 201210697011).
Chem., 2000, 112, 1861; (b) D. E. Chavez, S. K. Hanson,
J. M. Veauthier and D. A. Parrish, Angew. Chem., 2013, 125,
7014.
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